Long-term antipsychotic and benzodiazepine use and brain volume changes in schizophrenia: The Northern Finland Birth Cohort 1966 study

Sanna Huhtaniska; Erika Jääskeläinen; Tuomas Heikka; Jani S Moilanen; Heli Lehtiniemi; Jussi Tohka; José V Manjón; Pierrick Coupé; Lassi Björnholm; Hannu Koponen; Juha Veijola; Matti Isohanni; Vesa Kiviniemi; Graham K Murray; Jouko Miettunen

doi:10.1016/j.pscychresns.2017.05.009

Long-term antipsychotic and benzodiazepine use and brain volume changes in schizophrenia: The Northern Finland Birth Cohort 1966 study

Psychiatry Res Neuroimaging. 2017 Aug 30:266:73-82. doi: 10.1016/j.pscychresns.2017.05.009. Epub 2017 May 20.

Authors

Affiliations

¹ Center for Life Course Health Research, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland; Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland. Electronic address: sanna.huhtaniska@oulu.fi.
² Center for Life Course Health Research, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland; Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland; Department of Psychiatry, Oulu University Hospital, P.O. Box 26, FIN-90029 Oulu, Finland.
³ Center for Life Course Health Research, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland.
⁴ Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland; Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland; Department of Psychiatry, Oulu University Hospital, P.O. Box 26, FIN-90029 Oulu, Finland.
⁵ A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland.
⁶ Instituto de Aplicaciones de las Tecnologías de la Información y de las Comunicaciones Avanzadas (ITACA), Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia, Spain.
⁷ Laboratoire Bordelais de Recherche en Informatique, Unité Mixte de Recherche CNRS (UMR 5800), PICTURA Research Group, France.
⁸ Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland; Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland.
⁹ Department of Psychiatry, University of Helsinki and Helsinki University Hospital, P.O. Box 22, University of Helsinki, Finland.
¹⁰ Center for Life Course Health Research, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland; Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland; Department of Psychiatry, Oulu University Hospital, P.O. Box 26, FIN-90029 Oulu, Finland.
¹¹ Department of Diagnostic Radiology, Oulu University Hospital, P.O. Box 50, FIN-90029 Oulu, Finland.
¹² Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Box 189, Cambridge CB2 2QQ, UK; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Site, Cambridge CB2 3EB, UK.
¹³ Center for Life Course Health Research, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland; Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland.

PMID: 28618327
DOI: 10.1016/j.pscychresns.2017.05.009

Abstract

High doses of antipsychotics have been associated with loss in cortical and total gray matter in schizophrenia. However, previous imaging studies have not taken benzodiazepine use into account, in spite of evidence suggesting adverse effects such as cognitive impairment and increased mortality. In this Northern Finland Birth Cohort 1966 study, 69 controls and 38 individuals with schizophrenia underwent brain MRI at the ages of 34 and 43 years. At baseline, the average illness duration was over 10 years. Brain structures were delineated using an automated volumetry system, volBrain, and medication data on cumulative antipsychotic and benzodiazepine doses were collected using medical records and interviews. We used linear regression with intracranial volume and sex as covariates; illness severity was also taken into account. Though both medication doses associated to volumetric changes in subcortical structures, after adjusting for each other and the average PANSS total score, higher scan-interval antipsychotic dose associated only to volume increase in lateral ventricles and higher benzodiazepine dose associated with volume decrease in the caudate nucleus. To our knowledge, there are no previous studies reporting associations between benzodiazepine dose and brain structural changes. Further studies should focus on how these observations correspond to cognition and functioning.

Keywords: Antipsychotics; Benzodiazepines; Brain; MRI; Schizophrenia.

MeSH terms

Adult
Antipsychotic Agents / adverse effects*
Benzodiazepines / adverse effects*
Brain* / diagnostic imaging
Brain* / drug effects
Brain* / pathology
Caudate Nucleus* / diagnostic imaging
Caudate Nucleus* / drug effects
Caudate Nucleus* / pathology
Cohort Studies
Female
Finland
Humans
Magnetic Resonance Imaging
Male
Schizophrenia* / diagnostic imaging
Schizophrenia* / drug therapy
Schizophrenia* / pathology

Substances

Antipsychotic Agents
Benzodiazepines